The central role of CD30L/CD30 interactions in allergic rhinitis pathogenesis in mice

Abstract

CD30 ligand (CD30L) plays an important role in the amplification and/or activation of effector CD41 T cells, irrespective of Th cell subset. To examine the role of CD30L in allergic rhinitis, we evaluated an OVA model of allergic rhinitis in CD30L knock out (KO) mice on a BALB/c background sensitized with OVA. Symptoms of allergic rhinitis such as eosinophil infiltration into the nasal mucosa were drastically diminished in OVAsensitized CD30L KO mice following intranasal challenge with OVA. The levels of OVAspecific IgE in the sera and the Th2 response in nasopharynx-associated lymphoid tissues and cervical LNs of CD30L KO mice were significantly lower than those of WT mice following intranasal challenge with OVA. Intranasal administration of CD30-Ig during the effector phase with OVA significantly prevented the development of allergic rhinitis in WT mice. These results suggest that CD30L plays an important role in allergic rhinitis and that the inhibition of CD30L/CD30 signaling might be useful as a novel biological therapy for allergic rhinitis. during the allergic response, the induction phase and effector phase [17][18][19]. In the induction phase, Th2 cells and IgE specific for the allergen are generated in secondary lymphoid tissues. In the effector phase, allergic inflammation occurs in nasal mucosa and is further divided into two reactions: early-phase reaction and late-phase reaction. The early-phase reaction is characterized by sneezing, pruritus, nasal obstruction, and rhinorrhea, which are mediated by mast cells bound with IgE. The late-phase reaction is characterized with nasal congestion, inflammatory cells including basophils, eosinophils, mast cells, mononuclear cells, and neutrophils infiltration mediated by Th2 responses in mucosa and nasopharynx-associated lymphoid tissues (NALT) [20][21][22][23][24].In the present study, to investigate the effect of CD30/CD30L signal on the development of allergy rhinitis, the allergic rhinitis mouse model was investigated using CD30L KO mice. We showed that CD30L positively modulates the allergic symptoms and CD4 1 Th2 cell responses during the effector phase. Based on this result, the feasibility of CD30-Ig as an application in the treatment of allergic rhinitis has been confirmed. Implication of these findings for therapeutic application of CD30L/CD30 modulation for allergic rhinitis are discussed. Results CD30L KO mice showed impaired allergic inflammation in allergic rhinitisWe assessed the role of CD30L in a mice model of allergic rhinitis [25][26][27]. WT mice and CD30L KO mice were sensitized with OVA (25 mg) or PBS/aluminum hydroxide hydrate gel (alum) three times at 1-wk intervals, and then, from day 21 to day 35 after the first sensitization with OVA; mice were i.n. challenged with 20 mL of PBS or OVA (20 mg/mL) in the bilateral nostrils (Fig. 1A). Over a 5-min period after the last nasal drop of OVA or PBS, we counted the frequencies of sneeze and nasal rubbing of each mouse. The frequencies of nasal rubbing and sneezes after OVA challenge were si...

Cytosine–phosphate–guanosine-DNA induces CD274 expression in human B cells and suppresses T helper type 2 cytokine production in pollen antigen-stimulated CD4-positive cells

“…CD30L plays an important role in allergic rhinitis. Symptoms of allergic rhinitis, levels of antigen‐specific IgE in the sera and the Th2 response in lymphoid tissues were diminished drastically in antigen‐sensitized CD30L knock‐out mice following intranasal challenge with antigen [13]. CpG‐B not only induced the expression of PD‐L1 that inhibited Th2 cytokines, but also reduced the expression of B7RP‐1 and CD30L, which could promote Th2 inflammatory responses.…”

Cytokines as potential biomarkers of liver toxicity induced by Dioscorea bulbifera L.

“…Recently, the interaction of CD30/CD30L was reported to play some role in the crosstalk between natural killer and dendritic cells, and is critical for humoral immunity (26,27). Meanwhile, some studies demonstrate that CD30L/CD30 might be useful as a novel biological therapy for allergic rhinitis, inflammatory bowel disease, autoimmune diabetes, and chronic inflammatory skin diseases like psoriasis or atopic dermatitis (28)(29)(30)(31). However, there is no report about whether there is some role of CD30L in liver injury.…”

γδ T Lymphocytes Coordinate Eosinophil Influx during Allergic Responses

“…Interestingly, a large part of these cells (∼50%) expressed the CD30 molecule, a marker of T helper type 2 (Th2) cells (Romagnani et al, 1995; D’Elios et al, 1997; Fuchiwaki et al, 2011), produced high amounts of IL-4 (but not IFN-γ) and expanded in vitro under specific allergen stimulation, suggesting the existence and the local in vivo expansion of a Th2-type allergen-specific γδ T lymphocyte in the inflamed lungs of bronchial asthma patients, suggesting a role of these cells in local immune response to inhaled allergens.…”